Apatinib inhibits the growth of small cell lung cancer via a mechanism mediated by VEGF, PI3K/Akt and Ki‐67/CD31

Zhong, Ning; Zhuang, Wei; Huang, Qian; Wang, Qiang; Jin, Wenjian

doi:10.1111/jcmm.16926

Cited by 18 publications

(8 citation statements)

References 35 publications

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“…Apatinib is a novel selective vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, which is currently a targeted drug with a wide range of clinical applications. It mainly inhibits endothelial cell proliferation, cuts off tissue nutrient supply, and realizes antitumor function by competitively inhibiting the expression of the VEGFR-2 and blocking the binding of the VEGFR-2 and the VEGF to generate signal transduction [ 16 ]. In addition to its antiangiogenic effect, apatinib can enhance chemosensitization by reversing multidrug resistance.…”

Section: Discussionmentioning

confidence: 99%

[Retracted] Apatinib plus Radiotherapy on the Expression of CEA and VEGF in Advanced Oligometastatic Non‐Small‐Cell Lung Cancer

Zhu

2023

Evidence-Based Complementary and Alternative Medicine

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Objective. The purpose of this study was to evaluate the clinical efficacy of apatinib plus concurrent radiotherapy on carcinoma embryonic antigen (CEA) and vascular endothelial growth factor (VEGF) expression in patients with non-small-cell lung cancer (NSCLC) with oligometastases. Methods. This is a prospective randomized controlled trial. Sixty-four patients with oligometastatic NSCLC who were treated in the Central South University Xiangya School of Medicine Affiliated Haikou Hospital from January 2017 to January 2019 were randomly assigned into the control group and the study group, with 32 cases in each group. The control group was treated with stereotactic body radiotherapy (SBRT), and the study group was treated with apatinib. Results. The overall response rate (ORR) of the study group was significantly higher than that of the control group. The carcinoma embryonic antigen (CEA) and the vascular endothelial growth factor (VEGF) in the two groups were significantly decreased, with lower results in the study group compared to the control group. The 12-month and 24-month overall survival (OS) of the study group were significantly higher than those of the control group. There was no significant difference in progression-free survival (PFS) between the two groups. The median OS in the control group was 20.0 months, and the study group had not yet reached the median OS; the OS in the study group was significantly higher than that in the control group. There was no significant difference in adverse reactions between the two groups. Conclusion. For patients with oligometastatic lung cancer, apatinib combined with chemotherapy can significantly improve clinical efficacy, reduce tumor marker expression, and extend overall survival with good safety profiles.

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Section: Discussionmentioning

confidence: 99%

[Retracted] Apatinib plus Radiotherapy on the Expression of CEA and VEGF in Advanced Oligometastatic Non‐Small‐Cell Lung Cancer

Zhu

2023

Evidence-Based Complementary and Alternative Medicine

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“…Apatinib has been demonstrated to exert an active anti-tumor effect on SCLC, not only in vitro and in vivo research (28), but also in several clinical trials in ES-SCLC (29)(30)(31)(32). When used alone, apatinib achieved an ORR of 17.5% in per-protocol population with a median PFS of 3.0 months and a median OS of 5.8 months in thirdline or beyond treatment of ES-SCLC (29).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of apatinib as second or later-line therapy in extensive-stage small cell lung cancer: a prospective, exploratory, single-arm, multi-center clinical trial

Liu¹,

Xu²,

Xu³

et al. 2022

Transl Lung Cancer Res

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Background: A paucity of strategies exist for extensive-stage small cell lung cancer (ES-SCLC) patients who fail the first-line chemotherapy. Apatinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptor-2 (VEGFR-2), which has been demonstrated to have active antitumor activity in ES-SCLC when used only or combined with PD-1 inhibitors or chemotherapy with good tolerance. However, the efficacy and safety of apatinib monotherapy is unclear in second-line or beyond treatment of ES-SCLC.Methods: In this prospective, exploratory, single-arm, multi-center study, eligible patients were aged 18 years or older with histologically confirmed ES-SCLC, and had progressed on, or were intolerant to previous systemic treatment. Patients received apatinib 500 mg (orally qd, every 4 weeks a cycle). The efficacy was assessed after 1 cycle and then every 2 cycles based on computed tomography imaging per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). The primary endpoint was progressionfree survival (PFS). The adverse events (AEs) were assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 (NCI-CTCAE 4.0). This study is registered in the Chinese Clinical Trial Registry, number ChiCTR-OPC-17013964.Results: From 28 July 2017 to 21 June 2019, 62 patients were screened for eligibility, among whom 57 patients were available for efficacy and safety analysis. The objective response rate (ORR) was 14.3% and disease control rate (DCR) was 79.6%. The median PFS was 5.6 months [95% confidence interval (CI): 3.3-8.0 months] and the median overall survival (OS) was 11.2 months (95% CI: 7.5-24.0 months). Among the participants who received apatinib as second-line treatment, the median PFS and OS were 6.1 months (95% CI: 2.6-7.6 months) and 12.0 months (95% CI: 7.9 months to not reached), respectively. The most common AEs of all grades were anemia (36.8%), hypertension (33.3%), fatigue (31.6%), blood bilirubin increased (22.8%), elevated transaminase (19.3%), and hand-foot syndrome (17.54%). Grade 3 AEs included 2 (3.5%) cases of hypertension and 1 (1.8%) case of fatigue. No grade 4/5 AEs were observed.Conclusions: Apatinib showed encouraging anti-tumor activity in pretreated ES-SCLC patients with tolerable toxicities. Further larger scale studies are warranted to demonstrate the efficacy of apatinib.

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“… 26 And apatinib can also inhibit the growth of SCLC by affecting several pathway‐mediated mechanisms, such as PI3K/Akt and Ki‐67/CD31. 27 In addition, one of the reasons for chemoresistance is that transport proteins on the cell membrane will expel chemotherapeutic drugs that enter the interior of tumor cells. 28 Studies have shown that when apatinib is used in combination with chemotherapy drugs, it can significantly inhibit the efflux function of transporters, increase the sensitivity of drug‐resistant cells to drugs, even reverse the multidrug resistance of cells, and enhance the anti‐tumor efficacy of drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding the potential mechanism of this combination therapy, firstly, since VEGF plays a key role in angiogenesis and apatinib could exert its antigenic effect by inhibiting its induced endothelial cell proliferation and migration by targeting VEGFR2 with high selectivity 26 . And apatinib can also inhibit the growth of SCLC by affecting several pathway‐mediated mechanisms, such as PI3K/Akt and Ki‐67/CD31 27 . In addition, one of the reasons for chemoresistance is that transport proteins on the cell membrane will expel chemotherapeutic drugs that enter the interior of tumor cells 28 .…”

Section: Discussionmentioning

confidence: 99%

A phase II study of antiangiogenic therapy (Apatinib) plus chemotherapy as second‐line treatment in advanced small cell lung cancer

Wang

Sun

et al. 2022

Cancer Medicine

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Introduction Currently, only a few options are available for the treatment of patients with small‐cell lung cancer (SCLC) after the failure of first‐line platinum‐based chemotherapy. The present study aimed to evaluate the efficacy and safety of apatinib plus chemotherapy for second‐line treatment of advanced SCLC. Patients and Methods This prospective clinical trial recruited patients treated with apatinib plus second‐line chemotherapy until disease progression or intolerable toxicity. Logrank test power analysis was used for calculating samples. The primary endpoint was progression‐free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results A total of 29/31 enrolled patients were available for response evaluation until October 2019. The ORR and DCR were 27.59% (8/29) and 96.55% (28/29), respectively. The median PFS and OS were 7.36 months and 14.16 months, respectively, indicating better efficacy compared with the standard second‐line chemotherapies. The most common adverse events (AEs) were neutropenia (41.94%, 13/31), followed by leucopenia (35.48%, 11/31) and thrombocytopenia (25.81%, 8/31). The grade 3–4 AEs occurred in 12 (38.71%) patients, of which neutropenia (19.35%, 6/31), leucopenia (9.68%, 3/31), and proteinuria (6.45%, 2/31) were most common. Patients receiving an initial dose of apatinib 250 mg had a better tolerance. Conclusion Antiangiogenic therapy plus chemotherapy had encouraging efficacy in advanced SCLC patients, which provides an insight into the current status of second‐line therapy in SCLC.

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Apatinib inhibits the growth of small cell lung cancer via a mechanism mediated by VEGF, PI3K/Akt and Ki‐67/CD31

Cited by 18 publications

References 35 publications

[Retracted] Apatinib plus Radiotherapy on the Expression of CEA and VEGF in Advanced Oligometastatic Non‐Small‐Cell Lung Cancer

[Retracted] Apatinib plus Radiotherapy on the Expression of CEA and VEGF in Advanced Oligometastatic Non‐Small‐Cell Lung Cancer

Efficacy and safety of apatinib as second or later-line therapy in extensive-stage small cell lung cancer: a prospective, exploratory, single-arm, multi-center clinical trial

A phase II study of antiangiogenic therapy (Apatinib) plus chemotherapy as second‐line treatment in advanced small cell lung cancer

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